Menopause & PD

DR. ROBERTA MARONGIU is an Assistant Professor of Neuroscience at Weill Cornell Medicine in New York City. Dr. Marongiu received an APDA research grant in 2018 to understand the brain mechanisms that influence the differences in the onset and course of Parkinson’s disease (PD) between men and women. Pre-menopausal women have about a 2-fold reduced risk of developing PD as compared to men and post-menopausal women of similar age. Early menopause, either natural or surgical, is associated with an increased risk of PD. Menopausal women who had received estrogen are less likely to develop PD than those who had not. This suggests that gonadal hormones play an important role in protecting against PD. However, the mechanisms underlying the protective role of gonadal hormones, especially estrogen, against PD progression remain unclear. Dr. Marongiu is using a mouse model of PD with high levels of alpha-synuclein in the substantia nigra, and characterizing the effects of inducing menopause on PD pathology and clinical manifestations. The proposed work will help to clarify the ways in which hormones influence PD onset and progression. A better understanding of these underlying molecular mechanisms can lead to better treatments and a cure for PD.

An Interview with APDA Researcher Dr. Roberta Marongiu

APDA is very selective and strategic in our research funding, and we are proud to support some of the brightest researchers who are at the forefront of this disease. We are excited about Dr. Marongiu’s current work and have asked her some questions so you can learn more about the work APDA is making possible.

Q: What is the overarching goal of your research? What do you hope to find out?

A: The overall goal of my research is to understand the contribution of menopause transition (peri-menopause) on the onset and progression of PD in terms of pathology (alpha-synuclein accumulation, substantia nigra neurodegeneration, chronic inflammation) and motor dysfunction. Our hypothesis is that peri-menopause accelerates the onset and progression of PD, and this should be reflected in early motor deficits and more severe pathology in our female mouse model of menopause compared to pre-menopausal females, and similar to what we would expect to observe in male mice. With a novel multidisciplinary approach, our work is the first to study the influence of perimenopause on PD progression, and an important step in the identification of its underlying molecular mechanisms.

Q: Could you describe how you perform your studies?

A: I use two novel mouse models. The first one is the mouse model of PD generated by injecting the gene for human alpha-synuclein into the substantia nigra of the mouse - specifically in the dopaminergic cells that are usually lost in human PD. This leads to accumulation of alphasynuclein in the substantia nigra which can cause neurodegeneration and motor deficits. The second one is the innovative model of accelerated ovarian failure (AOF), induced by injecting low doses of a toxin into the mice that can model the transitional process seen in human menopause. After inducing AOF in our PD mice, we measure the extent of motor deficits over time in three tasks that measure spontaneous motor activity. At the conclusion of these tests, we study the mouse brains to measure the accumulation of alpha-synuclein, the extent of nigral neurodegeneration and the chronic inflammatory response. These measurements are correlated with the extent of motor symptoms observed in the mice.

Q: Can you tell us a little bit about what you have found out so far?

A: The first phase of our study was to develop our mouse model of PD by injecting alpha-synuclein into the substantia nigra. The generation of this model is an important step for our research as it allows us to study the effect of AOF on neuronal damage in the substantia nigra.